Another intriguing finding with potential functional importance is that 1–2 days following repetitive non-contingent cocaine administration, NAc shell MSNs express a relatively large proportion of so-called silent synapses due to the insertion of NR2B-containing NMDARs (Huang et al., 2009). Because silent synapses contain NMDARs but no or very few AMPARs (Malenka and Nicoll, 1997), they are ideal substrates for LTP (Marie et al., 2005) and thus may importantly contribute to the increase in AMPAR surface expression and AMAPR/NMDAR ratios that occur during prolonged withdrawal periods. All of the findings reviewed thus far can be incorporated into a relatively simple model of the changes that occur in excitatory synaptic strength during different time periods of withdrawal/challenge injections from cocaine administration (Fig. 3). As recently pointed out (Russo et al., 2010), these correlate well with the cocaine-elicited structural changes in dendritic spines on NAc MSNs, and will be further discussed below.
